From that item we get this description about the emerging ADHD drugs safety issue:

The new warnings advise that there have been reports of suicide-related events in patients treated with ADHD drugs. The reports involved thoughts of suicide, suicide attempts, and in a very small number of cases, completed suicide. These events have been reported at various times during treatment, particularly at the start or during dose changes, and also after stopping the drug treatment....

New information has emerged since to suggest that the risk of suicidal thoughts and behaviours may apply to all other ADHD drugs. There is little evidence to establish that these drugs cause suicidal thoughts and behaviours, but it is possible that they may contribute to the risk.... [emphasis added]

The following is a list of some brand name ADHD drugs to which this warning about suicide-related events in patients applies:

Adderall XR (mixed salts amphetamine extended-release)

Biphentin (methylphenidate controlled release)

Concerta (methylphenidate extended release)

Dexedrine (dextroamphetamine sulfate)

Intuniv XR (guanfacine extended release)

Ritalin (methylphenidate)

Ritalin SR (methylphenidate extended release)

Strattera (atomoxetine) [the warning was added to this drug label back in 2005]

Vyvanse (lisdexamfetamine dimesylate)

The March 2015 update about important safety information concludes with this critical comment: "It is Health Canada's view that the benefits of these drugs in the effective management of ADHD continue to outweigh their risks."

We will continue to monitor the benefit - risk profile of ADHD drugs like Adderall, Concerta, Ritalin, and Strattera, as well as watch for any corresponding regulatory action by the FDA here in the US.

Based on prescriptions for these several medical conditions and others -- by means of so-called "off-label" prescribing -- Cymbalta became a blockbuster drug for Lilly after being approved by the FDA in 2004. The first generic versions of Cymbalta were approved by the FDA on December 11, 2013.

Discontinuation symptoms have been systematically evaluated in patients taking duloxetine. Following abrupt or tapered discontinuation in placebo-controlled clinical trials, the following symptoms occurred at 1% or greater and at a significantly higher rate in duloxetine-treated patients compared to those discontinuing from placebo: dizziness, headache, nausea, diarrhea, paresthesia, irritability, vomiting, insomnia, anxiety, hyperhidrosis, and fatigue.

During marketing of other SSRIs and SNRIs (serotonin and norepinephrine reuptake inhibitors), there have been spontaneous reports of adverse events occurring upon discontinuation of these drugs, particularly when abrupt, including the following: dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesias such as electric shock sensations), anxiety, confusion, headache, lethargy, emotional lability, insomnia, hypomania, tinnitus, and seizures. Although these events are generally self-limiting, some have been reported to be severe.

And, as regards these negative withdrawal "side effects" which patients have allegedly suffered when they stopped taking the antidepressant Cymbalta, there are claims of possible misconduct by Eli Lilly set forth in that same item:

1) Cymbalta discontinuation syndrome is more severe and much more widespread than acknowledged by Eli-Lilly 2) Lilly sales representatives and marketing materials do not adequately inform physicians about the likelihood and severity of discontinuation syndrome3) Lilly Direct-to-Consumer (DTC) advertizing [sic] is misleading related to the probability, severity and complexity of Cymbalta discontinuation4) Lilly has not developed and fielded a clinically proven protocol for safely discontinuing Cymbalta

Significantly, in a report published by the Institute for Safe Medical Practices (ISMP) in the October 2012 of edition of QuarterWatch we find apparent support for some of those claims. From a preview in the front of this QuarterWatch publication concerning that "Duloxetine (CYMBALTA) and Serious Withdrawal Symptoms" report by ISMP:

We investigated a signal for duloxetine (CYMBALTA) and serious withdrawal symptoms. In the first quarter of 2012, 48 case reports of withdrawal described an array of problems that included neurological effects such as paresthesia and dizziness, psychiatric problems such as crying, suicidal ideation, and anger, and other symptoms including effects on appetite and weight gain. Early clinical studies of abrupt discontinuation showed that withdrawal effects occurred in 40 to 50% of patients, that 10% of those were severe, and that approximately half had not resolved when side effects monitoring ended after one or two weeks....

In the full report we document a serious lapse in the system that ought to be providing complete information and clear warnings for patients and health professionals about the extensive withdrawal effects of the antidepressant duloxetine. The Medication Guide for patients gives no hint that withdrawal symptoms can affect half of those discontinuing duloxetine, and that many cases may be severe, persistent, or both. The prescribing information for physicians and pharmacists does not provide realistic schedules for dose tapering or a clear picture of the likely incidence of these reactions....

As a result of this situation, lawsuits have been filed against Eli Lilly by some patients alleging Cymbalta caused withdrawal reactions and injuries when they discontinued or attempted to stop using Cymbalta. These drug injury lawsuits also claim that Lilly failed to adequately warn doctors and patients about the withdrawal risks associated with Cymbalta.

Singulair (montelukast) has been marketed in Canada since 1997. In Canada Singulair is indicated for: (1) the prophylaxis and chronic treatment of asthma in patients 2 years of age or older; and, (2) the relief of symptoms of seasonal allergic rhinitis in patients 15 years of age and older when other treatments are not effective or not tolerated.

From the date of marketing to Jan. 31, 2009, Health Canada received 13 adverse reaction (AR) reports related to suicidality or self-injury suspected of being associated with the use of [Singulair (montelukast)]. Eight reports stated that the reaction abated after the dose was reduced or the drug was stopped. The reaction reappeared after the reintroduction of [Singulair] in 1 case. All but 1 of the reports were received by Health Canada after the FDA's early communication [in March 2008].

From the date of marketing to Jan. 31, 2009, Health Canada received 29 other AR reports relating to depression, hostility or psychosis suspected of being associated with the use of [Singulair (montelukast)]. In 19 cases, the reaction abated after [Singulair] was stopped or the dose was reduced. The reaction reappeared after the reintroduction of [Singulair] in 4 cases. Thirteen of the 29 reports were received by Health Canada after the FDA's early communication [in March 2008].

No deaths were reported in any of the cases discussed above. Twenty-six of the 42 reports involved patients under 18 years of age (age was not indicated in 5 reports).

This announcement was followed closely by a medical journal article, "Montelukast and psychiatric disorders in children.", which was published in the June 23, 2009 edition of Pharmacoepidemiology and Drug Safety. The Abstract for this new Singulair article starts with a relatively ominous line: "A signal has been raised concerning montelukast and adverse drug reactions (ADRs) in children."

This June 2009 Singulair medical journal article presents the findings of a study whose purpose was "to evaluate psychiatric ADRs during treatment with [Singulair (montelukast)] in children." For this purpose, a team of researchers from Department of Clinical Pharmacology and Regional Pharmacovigilance Centre, Sahlgrenska University Hospital, Göteborg, Sweden, analyzed all reports of psychiatric disorders during treatment with Singulair in children under age 18 in the Swedish ADR database SWEDIS for the period 1998 to 2007.

From the Abstract for this Swedish Singulair study concerning adverse reactions in children:

RESULTS: A total of 48 reports of psychiatric disorders in children during treatment with montelukast were found in SWEDIS. Reports appeared every year after registration. Psychiatric disorders reported more than once included nightmares (n = 15), unspecified anxiety (n = 11), aggressiveness (n = 11), sleep disorders (n = 10), insomnia (n = 3), irritability (n = 3), hallucination (n = 3), hyperactivity (n = 3), and personality disorder (n = 2). In 23 reports (48%), the child experiencing psychiatric ADRs was ADR was indicated in 35 reports. In 28 of these (80%), the time from exposure to ADR was less than 1 week. A statistical signal for psychiatric disorders appeared in the fourth quarter of 1998 (three reports, IC-value: 2.34, 95% lower confidence limit: 0.62).

These findings led the researchers to conclude that psychiatric adverse reactions can occur in children during their treatment with Singulair (montelukast), which indicated to them that "[f]urther studies are needed to establish the magnitude of the problem."

We agree that more research should be done, and soon, about the extent of Singulair possibly causing psychiatric disorders in children using this very popular asthma drug from Merck.

...highlighting the risk of serious neuropsychiatric symptoms in patients using these products. These symptoms include changes in behavior, hostility, agitation, depressed mood, suicidal thoughts and behavior, and attempted suicide. The added warnings are based on the continued review of postmarketing adverse event reports for varenicline and bupropion received by the FDA. These reports included those with a temporal relationship between the use of varenicline or bupropion and suicidal events and the occurrence of suicidal ideation and suicidal behavior in patients with no history of psychiatric disease.

This second item had some concise and helpful background information about the history of safety issues concerning Chantix, Wellbutrin, and Zyban:

FDA first informed the public about the possibility of serious neuropsychiatric symptoms with [Chantix] in the November 20, 2007 FDA Early Communication About an Ongoing Safety Review. A complete history of related communications on [Chantix] and [Wellbutrin / Zyban] can be found at: Varenicline (marketed as Chantix) Information. Since that time, information about serious neuropsychiatric symptoms in patients taking varenicline has been added to the POST-MARKETING EXPERIENCE section of the prescribing information.

As FDA received additional information the suggestion of a possible association between both varenicline and bupropion (which was evaluated as a comparator to varenicline) and serious neuropsychiatric symptoms, in both patients with and those without previous history of psychiatric illness, became more evident as its review progressed....

We will watch for corporate press releases from Pfizer (which sells Chantix) as well as GlaxoSmithKline (which sells Wellbutrin and Zyban) which might be issued to present the drug company's reaction to this FDA announcement about adding a black-box warning for neuropsychiatric side effects being added to their respective product's Package Insert, or label.

Feb. 16 (Bloomberg) -- Roche Holding AG, the Swiss drugmaker, must pay $25.16 million in damages to a former user of its Accutane drug who blamed the acne medicine for his inflammatory bowel disease, a New Jersey jury ruled.

Andrew McCarrell, 38, won the verdict today at a retrial in Atlantic City, New Jersey. An appeals court ordered the new trial after overturning a $2.62 million award he won in May 2007. McCarrell, a computer technician from Birmingham, Alabama, testified he got sick after taking the drug for acne in 1995. He needed five surgeries, including one to remove his colon....

Roche Holding AG, the world’s biggest maker of cancer drugs, is pulling its Accutane acne medicine from the U.S. market after juries awarded at least $33 million in damages to users who blamed the drug for bowel disease.

Roche notified the U.S. Food and Drug Administration today that it was withdrawing Accutane after a “reevaluation” of its product lines showed it faced serious challenges from generic competitors, company officials said in a statement.

“In addition, Roche has been faced with high costs from personal-injury lawsuits that the company continues to defend vigorously,” according to the statement.

About 13 million people have taken Accutane since it went on the market in 1982. The medication was Roche’s second-biggest selling drug before the patent expired in 2002 and rivals started selling generic versions. Roche’s prescription market share of the drug is now below 5 percent, the company said.

From the above information, the apparent reasons for this June 2009 Accutane recall are loss of market share and mounting personal injury lawsuits.

This brought to mind the Tequin recall by Bristol-Myers Squibb (BMS) in April 2006.

On September 2, 2008 the FDA issued a Notice entitled "Determination That TEQUIN (Gatifloxacin) Was Withdrawn From Sale for Reasons of Safety or Effectiveness" which provides (and confirms) the real reason that Bristol-Myers Squibb Co. (BMY) decided to pull Tequin from the U.S. market in the spring of 2006:

SUMMARY: The Food and Drug Administration (FDA) has determined that TEQUIN (gatifloxacin) Tablets, Injection, and Oral Suspension, were withdrawn from sale for reasons of safety or effectiveness. This determination means that FDA will not accept or approve abbreviated new drug applications (ANDAs) for gatifloxacin oral tablets, injection, or oral suspension that refer to any previously approved dosage forms and strengths of TEQUIN (gatifloxacin).

As you may recall, in April 2006 when the news first broke that Bristol-Myers had decided to stop selling Tequin -- an antibiotic which was increasingly associated with potentially fatal blood-sugar problems -- the drug company said a continuing decline in Tequin sales was its reason for deciding to stop selling Tequin.

Returning to the June 26 Bloomberg article and its headline which implicates the Accutane lawsuit losses as being the primary reason for Roche deciding to pull Accutane, there have been some recent developments in the Accutane litigation.

In mid-June a New Jersey Superior Court judge ruled that Roche could not name new experts in the retrial of Andrew McCarrell v. Hoffman-La Roche Inc., et al.(No. ATL-L-1951-03-MT, N.J. Super., Atlantic Co.), a personal injury case where the plaintiff had alleged Accutane caused his inflammatory bowel disease (IBD). I defer to a March 13, 2009 post on the Drug and Device Law blog, "Accutane: McCarrell Remanded For New Trial", concerning the appeal of this Accutane jury verdict for the plaintiff.

A better result in June 2009 for Roche came from the federal court system's 11th Circuit Court of Appeals, which upheld a summary judgment in favor of the drug company in a case where it was alleged that Accutane caused the son of U.S. Rep. Bart Stupak, D-Mich., to commit suicide. The essential ruling reportedly there was that the plaintiff failed to produce evidence that Hoffman-La Roche Inc. knew or should have known that Accutane could cause suicide without premonitory symptoms (Laurie A. Stupak v. Hoffman-La Roche Inc., et al., No. 07-15980, 11th Cir.; 2009 U.S. App. LEXIS 12482).

We will watch to see if more information comes out in the future which will explain why Roche decided to remove Accutane from the market in June 2009.

On June 12, 2009 the FDA announced that Singulair (montelukast) as well as some other less popular leukotriene inhibitors -- Accolate (zafirlukast) as well as Zyflo and Zyflo CR (zileuton) -- must start to include a warning on its package insert, or label, regarding an increased risk of neuropsychiatric events including suicide and depression.

The Food and Drug Administration (FDA) announced an investigation Wednesday examining a link between suicide and Merck's popular allergy and asthma drug, Singulair.

Concerns over "behavioral issues" with Singulair developed over the past year. Merck periodically updated the drug's labels to include warnings for tremors, depression and anxiety. FDA spokesperson Susan Cruzan said reports of suicides by "three or four" people who were taking Singulair prompted Merck to clarify suicide warnings on labels and patient information sheets in October 2007.

U.S. regulators on Tuesday said their review of clinical trials does not suggest Merck & Co's Singulair asthma drug or similar medicines cause suicide or suicidal thought, although the data were inadequate to draw a firm conclusion....

The agency also studied trials involving two other medicines that work by blocking inflammation-causing proteins called leukotrienes, AstraZeneca Pls's Accolate (zafirlukast) and Zyflo (zileuton) sold by Cornerstone Therapeutics Inc.

"Although these data do not suggest that [Singulair (montelukast), Accolate (zafirlukast) or Zyflo and Zyflo CR (zileuton)] are associated with suicide or suicidal behavior, these clinical trials were not designed specifically to examine neuropsychiatric events," the FDA said. "As a result, some events may not have been reported."

Concerns about a possible suicidal link have arrested sales growth of Singulair, Merck's biggest product with annual sales of almost $4.5 billion.

Leukotriene inhibitors must include a warning regarding increased risk of neuropsychiatric events including suicide and depression, according to the FDA.

The requirement applies to montelukast (Singulair), zafirlukast (Accolate), and zileuton (Zyflo and Zyflo CR). All are approved to treat asthma, and montelukast is also approved to treat symptoms of allergic rhinitis and to prevent exercise-induced asthma.

Upon completing a review of the agents in April, the FDA found reports of agitation, aggression, anxiousness, dream abnormalities and hallucinations, depression, insomnia, irritability, restlessness, suicide, suicidal ideation, and tremor associated with use of the drugs.

The FDA based its review on postmarket reports and clinical trial data submitted by the manufacturers of the drugs....

The FDA said physicians should consider discontinuing the medications if patients develop neuropsychiatric symptoms.

Now that the association between Singulair and neuropsychiatric events such as suicide and depression has been announced by the FDA, we expect there to be additional case reports about Singulair users experiencing these serious side effects.

As always, we encourage people with personal knowledge about serious side effects from Singulair use to submit a MedWatch report to the FDA. We also welcome Comments, here, from people who want to share with others their side-effect experiences, or that of a family member, while using Singulair.